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Background: Liver transplantation (LT) in the context of acute-on-chronic liver failure (ACLF) remains controversial. Therefore, we aimed to investigate 30-day and 1-year patient survival, 1-year graft survival and early allograft dysfunction (EAD) after LT in patients with ACLF and compare to a control population of patients without ACLF. Furthermore, we investigated the effect of ACLF grading and timing of LT on these post-transplant outcomes and the prognostic value of the Chronic Liver Failure consortium (CLIF-C) ACLF score. Methods: We conducted a retrospective analysis of prospectively collected data of patients who were transplanted from 2007 to 2019. ACLF patients were identified based on the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium criteria. Post-transplant outcomes were evaluated using Mann-Whitney U and Fisher’s exact tests, Kaplan-Meier curves and Cox regression models. Results: 446 patients were included in our analysis: 47 patients with ACLF and 399 patients without ACLF. Thirty-day patient survival was similar in both groups: 93.62% vs. 97.49% for the ACLF and non-ACLF group, respectively (P=0.148). Mean Model of Early Allograft Function (MEAF) score was higher in patients with ACLF than in patients without ACLF (5.15 vs. 4.39, P=0.0177). One-year patient survival was similar in patients with ACLF to patients without ACLF (89.4% vs. 92.4%, P=0.1126). No association was found between ACLF and post-transplant patient survival (HR 1.606; 95% CI: 0.889-2.901; P=0.1160) and graft survival (HR 1.453; 95% CI: 0.825-2.56; P=0.1956). The CLIF-C ACLF score did not predict post-transplant patient survival (HR 1.005; 95% CI: 0.936-1.08; P=0.8846) and graft survival (HR 1.000; 95% CI: 0.933-1.071; P=0.9961). Conclusion: Our study shows excellent 30-day and 1-year post-transplant patient survival in ACLF patients. This demonstrates and further confirms that LT provides a survival benefit in selected patients with ACLF, given the dismal prognosis without transplantation. The CLIF-C ACLF score was found not to be a predictor of post-transplant patient survival, further highlighting the need for an accurate prognostic tool to support clinicians in their decision-making process.